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| 研究生： |
陳若君 Chen, Jo-Chun |
|---|---|
| 論文名稱： |
Design and Synthesis of α-Ketoamides as Cathepsin S Inhibitors for Potential Anti-Invasion and Anti-Angiogenesis Therapies 設計及合成α-酮醯胺化合物作為可逆型組織蛋白酶S抑制劑及其在抗癌細胞侵襲及抗血管增生之活性評估 |
| 指導教授： |
林俊成
Lin, Chun-Cheng |
| 口試委員: | |
| 學位類別： |
博士 Doctor |
| 系所名稱： |
理學院 - 化學系 Department of Chemistry |
| 論文出版年： | 2009 |
| 畢業學年度： | 98 |
| 語文別： | 中文 |
| 論文頁數： | 283 |
| 中文關鍵詞： | 抑制劑 |
| 外文關鍵詞： | inhibitor |
| 相關次數： | 點閱：2 下載：0 |
| 分享至: |
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中文摘要
本研究論文主要是設計與合成□-酮醯胺可逆型Cat S的抑制劑，並進一步評估此類抑制劑在抗癌侵襲及抗血管增生之抑制活性。我們建立ㄧ套96孔酵素免疫分析盤合成法，可快速合成且有效率篩選α -羥基醯胺化合物。本論文總共篩選789個α -羥基醯胺化合物，進ㄧ步合成71個□-酮醯胺化合物，其中有51個化合物具有抑制Cat S活性之IC50 小於10 nM，以CL1-5和HUVEC遷移分析進一步篩選出有效化合物113及162。在體外抑制A2058黑色素細胞瘤細胞的侵襲、轉移及內皮細胞血管增生的實驗中，化合物113和162皆表現出極佳的抑制效果。本論文的另一部分是設計及合成小分子活性探針，探針的結構包含四個部分：結合基團、反應基團、鏈接區域及標記基團，將本論文所合成之探針192及193應用於標記癌細胞當中的Cat S，初步測試結果證實探針192可以成功標記基因表達之Cat S。藉由實驗室所發展之磁性奈米粒子可將Cat S由蛋白質混合物中專一性分離出來。
總結本論文成功合成出有效的□-酮醯胺可逆型Cat S的抑制劑，此抑制劑無論是在酵素及體外細胞的試驗當中都可以表現出極佳抑制瘤細胞的侵襲、轉移及內皮細胞血管增生的效果。另外也成功合成出可標記rCat S的小分子活性探針
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